Biology subjects

Hossain, M. A.

Publications and source records attributed to Hossain, M. A..

At least 19 recordsLinked to original sources

bioRxiv2026

Systemic control and inter-organ communication of ovarian aging

Whether ovarian aging is intrinsic and unidirectional or dynamically regulated by systemic context remains an open question for fertility and women's healthspan. To address it, we developed a mouse ovarian transcriptomic aging clock (OvaAge) and applied it, together with published transcriptomic, epigenetic and pathway-resolved DNA methylation (PathAge) clocks, multi-omic analyses and reproductive outcomes, to new reciprocal heterochronic ovary transplantation and parabiosis experiments. Ovarian molecular age shifted in both directions: aged ovaries became younger in young hosts and young ovaries became older in aged hosts, and in each case the shift was partial across transcriptomic, epigenetic and pathway-resolved measures. Ovaries from 13-month-old C57BL/6J donors supported full-term pregnancies and live births at 17-18 months of age when transplanted into young hosts, but not when transplanted into old hosts, and young ovaries supported live births in 17-18-month-old recipients. Donor ovary age altered the transcriptomic age of the uterus in both directions, while young ovaries also lowered the transcriptomic age of aged liver and brain, identifying the ovary as an active node within an inter-organ aging network. Across unilateral and bilateral transplantation and parabiosis, an older environment increased inflammatory gene expression in the ovary, whereas a younger environment reduced it and increased mitochondrial and biosynthetic programs. Integration of methylation, expression and cell-type markers linked these changes to declining oocyte-associated programs and an expanding stromal compartment enriched for multinucleated giant cells (MNGCs). MNGC-rich regions formed a reversibly remodeled, focally aged niche with distinct spatial metabolic features, and a related macrophage expression signature was detected in human ovaries. Together, these findings identify ovarian aging as a modular, bidirectionally plastic process that is regulated by the systemic environment and point to tractable intervention points.

systems biology↗

bioRxiv2026

Human Osteocytes Express MHC ClassII and Act as Non-classical Antigen-Presenting Cells During Bacterial Infection

Osteocytes are the most abundant cells in bone and are increasingly recognised not only for their role in skeletal remodelling and inflammatory signalling but also for their potential involvement in immune responses. In this study, we searched available gene expression datasets of human primary osteocyte-like cells exposed acutely to Staphylococcus aureus and identified significantly induced expression of key genes related to antigen processing and presentation. We then confirmed that human bone explant-derived osteoblastic cells, representative of a mature osteoblast-pre-osteocyte stage, expressed, as expected, high cell surface levels of major histocompatibility complex (MHC) Class I but also, low basal levels of the MHC Class II family member, HLA-DR. However, confocal imaging revealed high expression of MHC Class II molecules and the peptide-loading chaperone HLA-DM within the lysosomal compartments, consistent with canonical antigen-processing machinery. Differentiation towards a mature osteocyte phenotype increased MHC Class II protein levels and maintained expression of intracellular HLA-DM. Exposure of mature osteocyte-like cells to S. aureus further up-regulated both intracellular and cell surface MHC Class II expression. Demonstrative of antigen presenting cell functionality, S. aureus-exposed osteocytes induced autologous CD4+ T cell proliferation. Furthermore, MHC Class II expression in osteocytes was detected in bone sampled from patients with periprosthetic joint infections, providing evidence that these mechanisms operate in vivo. Together, our findings reveal that human osteocytes are capable of inducible MHC Class II-associated antigen presentation in response to bacterial challenge, pointing to a novel role for osteocytes in adaptive immune surveillance within bone.

immunology↗

bioRxiv2026

Quantification of bone loss, periosteal bone formation and novel histopathological changes in a mouse implant-related Staphylococcus aureus infection model

Implant-associated bone infection involves a complex interplay between pathogenic stimuli and host cell responses, yet analysis in preclinical models has typically relied on qualitative or semi-quantitative measures. We aimed to establish a quantified evaluation framework to define host-pathogen relationships in a preclinical implant infection model. Staphylococcus aureus-coated stainless-steel implants were inserted trans-cortically in mouse tibiae and bone changes recorded longitudinally by in vivo micro-CT. An automated segmentation task list was developed to independently isolate and quantify cortical, periosteal-reactive, and trabecular bone compartments. RGB trichrome histomorphometry was used to quantify bone matrix integrity, osteocyte lacunar geometry, and osteoclastic activity. Droplet digital PCR was used to determine absolute bacterial and host genome copy number. Infected implants produced marked reductions in trabecular bone volume fraction, number, and bone mineral density (BMD), together with decreased cortical bone volume fraction and increased cortical porosity, accompanied by significant elevations in periosteal bone volume fraction. Histologically, infected bone exhibited increased eroded surface indicative of osteoclastic resorption, extensive degraded bone matrix and pathological remodelling of osteocyte lacunae towards circularity, consistent with an osteocytic osteolysis response. Infection-induced changes to cortical bone structure correlated mostly with host cell rather than bacterial load; however, cortical BMD negatively correlated with the bacterial:host genome ratio. This multifaceted, quantified framework reveals distinct pathobiological effects of implant-associated infection on trabecular, cortical, and periosteal bone compartments, bone matrix and osteocyte and osteoclast populations, consistent with reports in human patients, suggesting that major pathological changes are driven by the host bone cell response to infection.

pathology↗

bioRxiv2026

Unveiling Common Molecular Signatures and Pathways in Psychiatric Disorders and Alcohol Use Disorder through Integrated Transcriptome Analysis

Research studies have demonstrated that persons who have Alcohol Use Disorder (AUD) exhibit a more severe progression of psychiatric disorders, indicating potential causal connections between AUD and psychiatric disorders. Identifying underlying risk variables between AUD and psychiatric problems continues to be challenging. To address these issues, we created a bioinformatics pipeline and employed network-based methods to discover genes that exhibit improper expression in both AUD and psychiatric disorders. The objective of our study was to identify common molecular pathways that may elucidate the relationship between AUD and psychiatric disorders. We identified 49 genes that were expressed differently in tissue samples of patients with both AUD and psychiatric disorders. The DAVID online platform was used to discover the most significant Gene Ontology (GO) keywords and metabolic pathways. It detected the involvement of immune response, chemokine activity, TNF signaling, IL-17 signaling, and prostaglandin signaling pathways among the common DEGs. In addition, eleven topological algorithms identified a single hub protein, specifically TTR, from the protein-protein interaction (PPI) network. Through regulatory network analysis, we identified four crucial transcription factors (TFs)--YY1, FOXC1, JUND, and GATA2--and seven miRNAs (e.g., hsa-mir-146a-5p, hsa-mir-20a-5p) that play vital roles in regulating the development of AUD and psychiatric disorders. These miRNAs may serve as potential therapeutic targets. Validation of the hub gene using ROC analysis indicated acceptable predictive performance. Our approach revealed several potential biomarkers and signaling pathways linking AUD with psychiatric disorders, offering new insights for diagnosis and treatment. HighlightsO_LIIntegration of genome-scale transcriptomic datasets with biomolecular networks identified key hub genes (TTR, SOCS3, CXCL10, MMP9, and C4A). C_LIO_LICommon transcription factors, including YY1, FOXC1, JUND, and GATA2, were uncovered as potential regulatory elements. C_LIO_LICritical miRNAs (hsa-miR-146a-5p, hsa-miR-20a-5p, hsa-miR-107, hsa-miR-124-3p, hsa-miR-138-5p, and hsa-miR-330-3p) were identified as key post-transcriptional regulators. C_LIO_LIHistone modification profiling revealed multiple modification sites in hub genes and transcription factors, linking them to Intellectual Disability, Bipolar Disorder, Schizophrenia, and Alcohol Use Disorder. C_LIO_LIProtein-drug interaction analysis highlighted 10 candidate compounds with potential therapeutic relevance for the identified markers across ID, Bipolar Disorder, Schizophrenia, and AUD. C_LI

bioinformatics↗

bioRxiv2026

Identifying Convergent Therapeutic Targets and Pathways for Post-Traumatic Stress Disorder, Schizophrenia And Bipolar Disorder via In Silico Approaches

ObjectiveThe objective of this study is to provide a concise overview of the various molecular problems and possible treatment targets that have been linked and associated with the onset of certain psychiatric diseases. MethodsObtaining the data from NCBI, we applied GREIN to analyze our datasets. The protein-protein interaction, gene regulatory network, protein-drug-chemical, gene ontology, and pathway network were constructed using STRING, Funrich and DAVID libraries. In order to display our suggested network, we utilized Cytoscape and R studio, verifying our hub gene using roc analysis. ResultsWe discovered a number of strong candidate hub proteins in significant pathways, namely out of 32 (HLA-DRA, HLA-A, HLA-B, HLA-DOB and BRD2) common genes. We also identified a number of TFs (FOXC1, NFYA, RELA, GATA2, FOXL1, SRF and NFIC); miRNA (hsa-mir-129-2-3p, hsa-mir-148b-3p, hsa-mir-196a-5p, hsa-mir-26a-5p, hsa-mir-27a-3p, hsa-mir-23b-3p, hsa-mir-500a-3p, hsa-mir-423-5p, hsa-miR-142-5p, and hsa-miR-671-5p) and chemicals (Estradiol, Antirheumatic Agents, Valproic Acid, Selenium, Vitamin E, ICG 001, Ifosfamide, Tetrachlorodibenzodioxin, arsenic trioxide, entinostat, sodium arsenite and Hydralazine) may control DEGs in transcription as well as post-transcriptional expression levels. ConclusionIn summary, our computational methods have identified distinct potential biomarkers that demonstrate the impact of PTSD, Schizophrenia, and BD on autoimmune inflammation and infectious diseases. Additionally, we have identified pathways and gene regulators through which these psychiatric disorders may affect biological processes. Graphical AbstractThe graphical abstract demonstrates the thorough strategy of combining systems biology and computational technologies to identify significant markers and pathways in blood tissues impacted by post-traumatic stress disorder, Schizophrenia, and Bipolar disorder. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=152 SRC="FIGDIR/small/708243v1_ufig1.gif" ALT="Figure 1"> View larger version (48K): org.highwire.dtl.DTLVardef@1cd13bforg.highwire.dtl.DTLVardef@cb6392org.highwire.dtl.DTLVardef@f634cforg.highwire.dtl.DTLVardef@532bd_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2025

N-Alkyl Sulfamates as a New Class of nsP2 Cysteine Protease Inhibitors with Broad Spectrum Antialphaviral Activity

The emergence of mosquito-borne alphaviruses that cause chronic arthritis or encephalitis underscores the urgent need for broad-spectrum antiviral therapeutics. The viral nsP2 cysteine protease, which is essential for alphavirus replication, is a promising antiviral target. Vinyl sulfone-based inhibitors, such as RA-2034, potently inhibit nsP2 protease but suffer from glutathione reactivity and species-dependent systemic clearance catalyzed by glutathione S-transferase. To address these liabilities, we explored alternative electrophilic warheads and identified reverse amide inhibitors bearing N-alkyl sulfamate warheads with improved biochemical and antiviral profiles. N-methyl sulfamate acetamide 5 emerged as a lead compound with potency against both New and Old World alphaviruses, low GSH reactivity, and high proteome-wide selectivity. Despite its promising antialphaviral activity, 5 exhibited rapid clearance due to hepatic glucuronidation. Structure-activity studies revealed modifications that improve metabolic stability while retaining antiviral activity. These findings introduce sulfamate acetamides as a new class of covalent nsP2 protease inhibitors and advance the discovery of direct acting pan-alphavirus drugs.

pharmacology and toxicology↗

bioRxiv2025

Phylogenetically-informed crayfish conservation in the face of climate change

Crayfish are an ancient clade of freshwater decapods that play vital and diverse ecological roles in the freshwater systems that they inhabit. One third of assessed crayfish species are threatened with extinction and 87% are highly sensitive to climate change. However, the extent to which the evolutionary history of crayfish is threatened, especially by climate change, remains unclear. To address this, we produced a phylogenetically-informed species prioritisation for the conservation of crayfish and explored the consequences of projected climate change scenarios on crayfish phylogenetic diversity. We used the EDGE2 metric to highlight 70 priority species for conservation. Their combined threatened evolutionary history accounts for 40.7% of the expected phylogenetic diversity loss for all 673 crayfish. Of these priority species, 45.7% are vulnerable to climate change, with the majority (32 species) located in Australia. Under a high warming scenario, individual species that are more evolutionarily distinct are projected to be disproportionately affected. The extinction of climate change vulnerable species could cause the loss of up to 26.3% more phylogenetic diversity than the random expectation, equivalent to 409 million years of evolutionary history. Our results highlight the need to consider climate change effects on phylogenetic diversity to fully understand its impact on biodiversity. If actions were taken to avoid a worst-case warming scenario in favour of an intermediate scenario, we could safeguard 251 million years of unique crayfish evolutionary history.

ecology↗

bioRxiv2025

Identification of a Broadly Acting Inhibitor of the Alphavirus Non-Structural Protein 2 Helicase

Alphaviruses are mosquito-borne viruses that have caused significant outbreaks in the 21st century. Despite multiple recent outbreaks, there are no approved antiviral drugs to treat any alphavirus infection. Therefore, developing broadly acting antiviral drugs effective against multiple alphaviruses is necessary and could provide protection from both current and emerging alphavirus threats. A critical component of the alphavirus replication complex is non-structural protein 2 (nsP2), which is a multifunctional enzyme containing a helicase domain connected to a protease domain by a flexible linker. nsP2 functions as an ATP-dependent helicase, is conserved across the alphavirus genus, and is essential for virus replication, making it a promising target for development of alphavirus broad-acting antiviral drugs. Previous studies identified an enantioselective compound RA-0025298 that inhibited nsP2 ATPase activity and chikungunya virus CHIKV replication. Antiviral testing of RA-25298. against a diverse group of alphaviruses found broad activity except for Sindbis-like viruses. Using this information along with mutational profiling of virus passaged with RA-0025298 we identified the site of RA-0025298 action and confirmed the binding site via biophysical analyses. Finally, we found that the active enantiomer of RA-0025298 (SGC-NSP2hel-1) reduced viral loads in vivo and protected mice from tissue damage and disease caused by CHIKV infection. These findings further describe the mechanism of action of a first-in-class nsP2 helicase inhibitor with the potential for development as a broad spectrum drug for treating or preventing disease caused by current and emerging alphaviruses. One Sentence SummaryThis study describes the mechanism of action and in vivo efficacy of a first in class broadly acting inhibitor of alphavirus nsP2 helicase activity.

microbiology↗

bioRxiv2025

An Enantioselective Chemical Probe for Chikungunya nsP2 Helicase with Antialphaviral Activity

Chikungunya virus (CHIKV) replication relies on the multifunctional nsP2 protein, making it an attractive target for antiviral drug discovery. Here, we report the resolution of oxaspiropiperidine 1, a first-in-class inhibitor of the CHIKV nsP2 RNA helicase (nsP2hel), into its constitutive enantiomers and characterization of their antiviral activity. The enantiomer (R)-1 exhibited potent inhibition of viral replication, nsP2hel ATPase activity, and dsRNA unwinding, while the (S)-1 enantiomer was >100-fold less active. The (R)-1 enantiomer also demonstrated high selectivity for CHIKV over other RNA viruses and for nsP2hel over other RNA helicases. Direct binding of (R)-1 to nsP2hel protein was confirmed by 19F NMR. Biophysical and structural studies revealed conformational polymorphism in the spirocyclic scaffold of (R)-1, suggesting a potential role of thermal mobility of the ligand in allosteric inhibition of nsP2hel. Collectively, these findings designate (R)-1 (RA-NSP2-1) as a high-quality chemical probe and (S)-1 (RA-NSP2-1N) as a negative control for probing the biology of alphavirus RNA helicases.

pharmacology and toxicology↗

bioRxiv2025

In Silico Evaluation and Therapeutic Targeting of LVDD9B Protein for WSSV Inhibition: Molecular and Ecological Insights for Aquaculture Solutions

BackgroundThis study aimed to investigate structural dynamics, binding interactions, stability, pharmacokinetics, ecological risks, and bioactivity of shrimp receptor protein LVDD9B to identify potential therapeutic candidates against White Spot Syndrome Virus (WSSV). MethodsLVDD9B proteins 3D structure was predicted using SWISS-MODEL and validated with ProSA and Ramachandran plots. Protein-protein docking between LVDD9B and VP26 (WSSV protein) was performed using HADDOCK 2.4 server. Molecular docking, dynamics simulations, binding-free energy calculations, principal component analysis (PCA), electrostatic, and vibrational frequency analyses evaluated binding affinity, stability and polarity of complexes. Results128-amino-acids of LVDD9B protein was predicted as predominantly cytoplasmic with stable, and hydrophilic, with structural analysis identified key secondary structures and conserved chitin-binding site. Docking studies revealed strong interactions between LVDD9B and VP26, supported by hydrogen-bonds and salt bridges. Molecular dynamics simulations demonstrated stable complexes with fluctuating RMSD values, and MM/GBSA calculations indicated favorable binding free energies. Pharmacokinetic analysis highlighted promising bioavailability and drug-like properties for Luteolin and Quercetin from Cuscuta reflexa, while ecological assessment identified Cosmosiin as least hazardous, with Quercetin and Luteolin showing higher toxicity. PCA revealed stable protein-ligand complexes with flexibility in Apo form. Isorhoifolin exhibited the lowest internal energy (-2099.4722 Hartree) and highest dipole moment (8.1833 Debye). Frontier orbital analysis showed HOMO-LUMO gaps (4.05-4.34 eV) influencing reactivity, while MEP and vibrational frequency analyses supported compound stability and bioactivity. ConclusionsThis study explores LVDD9Bs structural and interaction dynamics for developing antiviral therapy against WSSV, highlighting therapeutic potential of Cosmosiin, Isorhoifolin, Quercetin and Luteolin based on their pharmacokinetic and ecological profiles.

bioinformatics↗

bioRxiv2025

Assessment of the Anticancer Activity of Aegle marmelos Leaf Extracts Against Ehrlich's Ascites Carcinoma (EAC) Cell Line in Swiss Albino Mice

Cancer remains a significant health threat globally, and as a result, the demand for safer and more effective alternatives keeps growing. In this current study, we have assessed the anticancer activity of Aegle marmelos extract on Ehrlich Ascites Carcinoma (EAC) cells on Swiss Albino mice. Three extracts were prepared: a methanolic (APME), chloroform (APCE), and n-hexane (APHE) extract. These extracts were administered intraperitoneally in doses of 50 mg/kg and 100 mg/kg per dose on 6 consecutive days to mice. The anticancer activity was assessed from viable tumor cell count, with percentage (%) inhibition of cell growth, and changes in body weight of the mice that had been treated with extracts. Of all the extracts, APHE exhibited the most tumor growth inhibition (62.2% at 100 mg/kg), followed by APME (59.25%) and APCE (54.86%), compared to the standard chemotherapy drug doxorubicin (81.6% inhibition at 0.8 mg/kg/day). Mice treated with the extracts experienced less weight loss than the control group, with an approximate effect of 0.50 {+/-} 0.06 g/day. A Brine Shrimp Lethality Bioassay demonstrated a cytotoxic dose-dependent impact, with LC50 values of 18.38, 36.79, and 46.45 micrograms per milliliter for n-hexane, methanolic, and chloroform extracts, respectively. The tumor suppression and cytotoxicity effects of Aegle marmelos extracts are probably attributable to the bioactive compounds such as flavonoids, alkaloids, and essential oils that have known apoptotic and antiproliferative activities. The extracts were not as effective as doxorubicin; however, the extracts natural composition and ability to reduce weight loss due to cancer indicate potential to be used in combination with or as an alternative to cancer-treating medications. Further research includes that mechanistic studies and clinical trials are needed to confirm their therapeutic potential.

cancer biology↗

bioRxiv2025

Assessment of Meridic Gel Larval Diet and Meridic Adult Diet for Mass Rearing of Bactrocera dorsalis (Diptera: Tephritidae)

The oriental fruit fly, Bactrocera dorsalis (Diptera: Tephritidae), is a widespread pest in Bangladesh. Sterile Insect Technique (SIT) offers a solution for effectively suppressing this fruit fly species. However, SIT involves mass rearing of fruit fly species in a laboratory where a standardized artificial rearing diet is crucial for ensuring uniform growth, development, and reproduction. In this study, we assessed efficacy of a new formulated gelbased meridic larval diet as well as protein and carbohydrate rich adult diets for the rearing of B. dorsalis in a laboratory condition. Proximate analysis was conducted for our formulated rearing diets to determine the content of moisture, protein, fat, carbohydrate, and ash. Several key biological parameters, including egg hatching rate, pupation rate, pupal weight, adult emergence, adult growth, sex ratio, and flight capacity, were assessed. Statistical analysis using Tukey box plots revealed a significant improvement in adult body parameters and an increase in longevity for our formulated diets. In addition, our study presents survival analysis using non-parametric Kaplan-Meier estimator and Weibull parametric model. This study shows that integrating our formulated diets into the mass rearing process of B. dorsalis in a laboratory could significantly improve the production of larger and healthier flies on a large scale.

zoology↗

bioRxiv2025

Identification of Direct-acting nsP2 Helicase Inhibitors with Anti-alphaviral Activity

Alphaviruses are mosquito-borne RNA viruses that pose a significant public health threat, with no FDA-approved antiviral therapeutics available. The non-structural protein 2 helicase (nsP2hel) is an enzyme involved in unwinding dsRNA essential for alphavirus replication. This study reports the discovery and optimization of first-in-class oxaspiropiperidine inhibitors targeting nsP2hel. Structure-activity relationship (SAR) studies identified potent cyclic sulfonamide analogs with nanomolar antiviral activity against chikungunya virus (CHIKV). Biochemical analyses of nsP2hel ATPase and RNA unwindase activities showed these compounds act by a non-competitive mode suggesting that they are allosteric inhibitors. Viral resistance mutations mapped to nsP2hel and a fluorine-labeled analog exhibited direct binding to the protein by 19F NMR. The lead inhibitor, 2o, demonstrated broad-spectrum antialphaviral activity, reducing titers of CHIKV, Mayaro virus (MAYV), and Venezuelan equine encephalitis virus (VEEV). These findings support nsP2hel as a viable target for development of broad-spectrum direct-acting antialphaviral drugs. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=108 SRC="FIGDIR/small/641060v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@856df5org.highwire.dtl.DTLVardef@1f6225borg.highwire.dtl.DTLVardef@4997d5org.highwire.dtl.DTLVardef@18f42f2_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗

bioRxiv2025

Computational investigation unveils pathogenic LIG3 non-synonymous mutations and therapeutic targets in acute myeloid leukemia

Single nucleotide polymorphisms (SNPs) in DNA repair genes can impair protein structure and function, contributing to disease development, including cancer. Non-synonymous SNPs (nsSNPs) in the LIG3 gene are linked to genomic instability and increased cancer risk, particularly acute myeloid leukemia (AML). This study aims to identify the most deleterious nsSNPs in the LIG3 gene and potential therapeutic targets for DNA repair restoration in AML. We employed in-silico computational methods to analyze LIG3 nsSNPs, using PredictSNP and Mutation3D to assess pathogenicity. Subsequently, molecular docking and dynamics simulations were conducted to evaluate ligand-binding affinities and protein stability. Out of the 12,191 mapped SNPs, 132 were nsSNPs located in the coding region. Among these, 18 nsSNPs were identified as detrimental including 12 destabilizing and 6 stabilizing nsSNPs. Nine cancer-associated nsSNPs, including L381R and R528C, were predicted due to their structural and functional impacts. Further analysis revealed key phosphorylation and methylation sites, such as 529S and 224R. Molecular dynamics simulations highlighted stable interactions of compounds AHP-MPC and DM-BFC with wild-type and R528C mutant LIG3 proteins, while R671G and V781M mutants showed instability. Protein-protein interaction networks and functional enrichment linked LIG3 to DNA repair pathways. Kaplan-Meier analysis associated high LIG3 expression with improved survival in breast cancer and AML, suggesting its role as a prognostic biomarker. This study emphasizes the mutation-specific effects of LIG3 nsSNPs on protein stability and ligand interactions. We recommend identifying DM-BFC to advance personalized medicine approaches for targeting deleterious variants, following in vitro and in vivo validation for AML treatment.

cancer biology↗

bioRxiv2025

Impact of Soil Salinity on Microbial Community Composition in Coastal Agricultural lands of Bangladesh: A Metagenomic Approach

A significant obstacle to agricultural productivity is soil salinity, especially in coastal areas where the problem is made worse by climate change and rising sea levels. This study investigates the impact of salinity on microbial community structure and function in agricultural soils from Kuakata, Bangladesh, using 16S rRNA metagenomic sequencing technique. Both saline (EC > 4 dS/m) and non-saline (EC < 1.5 dS/m) areas had soil samples taken; saline soils showed symptoms of crop stress, such as yellowing and blackish discoloration. In comparison to their non-saline counterparts, our investigation showed that saline soils had much reduced microbial diversity and different community compositions. Both soil types were dominated by Proteobacteria and Chloroflexi, while saline soils displayed an enrichment of anaerobic texa (e.g., Desulfobacterota, Pseudomonas) and sulfate-reducing bacteria (e.g., Desulfobacterota, Deferrisomatota). Interestingly, saline soils had a much larger percentage of anaerobic microorganisms (36.4%) than non-saline soils (29.3%) which might results in enhanced denitrification, sulphate reduction, and hydrogen sulphide buildup. These processes disrupt nutrient cycling, lower organic matter decomposition and create toxic conditions for plant growth, ultimately contributing to crop failure. This study provides an insight into the distinct microbial composition in saline and non-saline samples, which can assist in understanding the role of microbial populations in agriculture in saline environments.

microbiology↗

bioRxiv2025

Species Dependent Metabolism of a Covalent nsP2 Protease Inhibitor with in Vivo Anti-alphaviral Activity

RA-0002034 (1) is a potent covalent inhibitor targeting the alphavirus nsP2 cysteine protease. The species-dependent pharmacokinetics and metabolism of 1 were investigated to evaluate its therapeutic potential. Pharmacokinetic profiling revealed rapid clearance in mice, predominantly mediated by glutathione S-transferase (GST)-catalyzed conjugation. This metabolic liability contrasted with slower clearance observed in human hepatocytes and preclinical species such as rats, dogs, and monkeys. Cross-species studies confirmed the dominance of GST-driven metabolism in mice, whereas oxidative pathways were more pronounced in dogs. Despite rapid systemic clearance, 1 achieved antiviral efficacy in mice, reducing CHIKV viral loads in multiple tissues. Initial estimations of human hepatic clearance and half-life extrapolated from animal data indicate that b.i.d. dosing of 1 will be possible to maintain concentrations sufficient for antiviral activity in humans. These cross-species pharmacokinetic and metabolism studies support the continued evaluation of 1 as a promising anti-alphaviral therapeutic. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=61 SRC="FIGDIR/small/632788v1_ufig1.gif" ALT="Figure 1"> View larger version (14K): org.highwire.dtl.DTLVardef@8c1558org.highwire.dtl.DTLVardef@cd7e21org.highwire.dtl.DTLVardef@113e88aorg.highwire.dtl.DTLVardef@7c7dc_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗

bioRxiv2024

Identification of Inhibitors of Chikungunya virus nsP2 ATPase

Non-structural protein 2 (nsP2), which plays an essential role in replication of CHIKV, contains a protease, helicase, and methyltransferase-like domain. We executed a simple a screen using malachite green to detect compounds that decreased ATP hydrolysis and tested a library of diverse compounds to find inhibitors of CHIKV nsP2 helicase.

biochemistry↗

bioRxiv2024

Prevalence of Key Spike Protein Mutations and Their Limited Effect on COVID-19 Clinical Manifestations in Sylhet, Bangladesh

SARS-CoV-2 is the virus responsible for the COVID-19 pandemic, which has spread rapidly around the world and had a significant impact on public health and the economy worldwide. This study investigated the correlation between SARS-CoV-2 spike protein mutations, clinical outcomes and patient demographics in the Sylhet region of Bangladesh. We looked at the full genome sequences of 37 SARS-CoV-2 samples that were collected between January and June 2020. Specifically, we looked at five major spike protein mutations: D614G, A570D, D1118H, A222V, and P681R. The D614G mutation was the most prevalent (94.6%), followed by A570D and D1118H (both 32.4%), A222V (29.7%), and P681R (13.5%). Despite their high prevalence, we found no statistically significant associations between these mutations and clinical outcomes or demographic variables, except for possible trends for the P681R mutation. We found that age played a decisive role in recovery from COVID-19, with older patients exhibiting slower recovery rates. In terms of predictors of outcome, gender differences were observed: clinical symptoms and viral genetic mutations were more influential for men, while age and disease progression were more important for women. Common nucleotide substitutions (A23403G, C3037T, and C14408T) associated with European strains were identified, suggesting possible routes of transmission. This study contributes to our understanding of the genetics, clinical manifestations and epidemiology of SARS-CoV-2 in the Sylhet region and emphasizes the need for continuous genomic surveillance and adaptive public health strategies.

microbiology↗